PE20011294A1 - PHARMACEUTICAL COMPOSITIONS OF ESTROGEN AGONISTS / ANTAGONISTS AND STATINES TO TREAT OSTEOPOROSIS AND REDUCE CHOLESTEROL - Google Patents
PHARMACEUTICAL COMPOSITIONS OF ESTROGEN AGONISTS / ANTAGONISTS AND STATINES TO TREAT OSTEOPOROSIS AND REDUCE CHOLESTEROLInfo
- Publication number
- PE20011294A1 PE20011294A1 PE2001000079A PE2001000079A PE20011294A1 PE 20011294 A1 PE20011294 A1 PE 20011294A1 PE 2001000079 A PE2001000079 A PE 2001000079A PE 2001000079 A PE2001000079 A PE 2001000079A PE 20011294 A1 PE20011294 A1 PE 20011294A1
- Authority
- PE
- Peru
- Prior art keywords
- phenyl
- alkyl
- reduce cholesterol
- statines
- antagonists
- Prior art date
Links
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/473—Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/30—Oestrogens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Physical Education & Sports Medicine (AREA)
- Diabetes (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
SE REFIERE A UNA COMPOSICION QUE COMPRENDE: a)UN AGONISTA O ANTAGONISTA DE ESTROGENO DE FORMULA I DONDE A ES CH, NR; B, D Y E SON CH, N; Y ES FENILO, NAFTILO, CICLOALQUILO C3-C8, CICLOALQUENILO C3-C8, HETEROCICLO DE 5 MIEMBROS, ANILLO BICICLICO; Z1 ES (CH2)pW(CH2)q, O(CH2)pCR5R6, O(CH2)pW(CH2)q, ENTRE OTROS; G ES NR7R8, GRUPO a, AMINA BICICLICA; Z2 ES NH, O, S, CH2; W ES CH2, HC=CH, O, NR2, S(O)n, ENTRE OTROS; R ES H, ALQUILO C1-C6; R2 Y R3 SON H, ALQUILO C1-C4; R4 ES H, HALOGENO, ALQUILO C1-C6, ENTRE OTROS; R5 Y R6 SON ALQUILO C1-C8, FORMAN CARBOCICLO C3-C10; R7 Y R8 SON FENILO, ANILLO CARBOCICLO C3-C10, HETEROCICLO C3-C10, H; e Y n SON 0-2; m ES 1-3; p Y q SON 0-3; SIENDO UN COMPUESTO PREFERIDO (-)CIS-6-FENIL-5-[4-(2-PIRROLIDIN-1-ILETOXI)FENIL]-5,6,7,8-TETRAHIDRONAFTALEN-2-OL, TAMOXIFENO, RALOXIFENO, ENTRE OTROS; b)UNA ESTATINA TAL COMO SIMVASTATINA, PRAVASTATINA, CERIVASTATINA, MEVASTATINA, LOVASTATINA, ATORVASTATINA, ENTRE OTROS. LA COMPOSICION PUEDE SER UTIL PARA ESTIMULAR LA FORMACION DE HUESO; PREVENIR LA PERDIDA OSEA O REDUCIR COLESTEROL, TRATAR HIPERLIPIDEMIAREFERS TO A COMPOSITION THAT INCLUDES: a) AN AGONIST OR ANTAGONIST OF ESTROGEN OF FORMULA I WHERE A IS CH, NR; B, D AND E ARE CH, N; AND IT IS PHENYL, NAPHTHYL, C3-C8 CYCLOALKYL, C3-C8 CYCLOALKENYL, 5-MEMBER HETERO CYCLE, BICYCLE RING; Z1 IS (CH2) pW (CH2) q, O (CH2) pCR5R6, O (CH2) pW (CH2) q, AMONG OTHERS; G IS NR7R8, GROUP a, BICYCLIC AMINE; Z2 IS NH, O, S, CH2; W IS CH2, HC = CH, O, NR2, S (O) n, AMONG OTHERS; R IS H, C1-C6 ALKYL; R2 AND R3 ARE H, C1-C4 ALKYL; R4 IS H, HALOGEN, C1-C6 ALKYL, AMONG OTHERS; R5 AND R6 ARE C1-C8 ALKYL, FORMING C3-C10 CARBOCYCLE; R7 AND R8 ARE PHENYL, C3-C10 CARBOCYCLE RING, C3-C10 HETEROCYCLE, H; and Y n ARE 0-2; m IS 1-3; p and q ARE 0-3; BEING A PREFERRED COMPOUND (-) CIS-6-PHENYL-5- [4- (2-PYRROLIDIN-1-ILETOXI) PHENYL] -5,6,7,8-TETRAHIDRONAFTALEN-2-OL, TAMOXIFENO, RALOXIFENO, AMONG OTHERS ; b) A STATIN SUCH AS SIMVASTATIN, PRAVASTATIN, CERIVASTATIN, MEVASTATIN, LOVASTATIN, ATORVASTATIN, AMONG OTHERS. THE COMPOSITION MAY BE USEFUL TO STIMULATE BONE FORMATION; PREVENT BONE LOSS OR REDUCE CHOLESTEROL, TREAT HYPERLIPIDEMIA
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US18892300P | 2000-01-26 | 2000-01-26 | |
US20532700P | 2000-04-21 | 2000-04-21 |
Publications (1)
Publication Number | Publication Date |
---|---|
PE20011294A1 true PE20011294A1 (en) | 2001-12-21 |
Family
ID=26884589
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PE2001000079A PE20011294A1 (en) | 2000-01-26 | 2001-01-24 | PHARMACEUTICAL COMPOSITIONS OF ESTROGEN AGONISTS / ANTAGONISTS AND STATINES TO TREAT OSTEOPOROSIS AND REDUCE CHOLESTEROL |
Country Status (12)
Country | Link |
---|---|
US (2) | US6756401B2 (en) |
EP (1) | EP1123717A3 (en) |
JP (1) | JP2001206845A (en) |
KR (1) | KR20010083135A (en) |
AU (1) | AU780568B2 (en) |
CA (1) | CA2332214A1 (en) |
CO (1) | CO5251465A1 (en) |
HU (1) | HUP0100388A3 (en) |
IL (1) | IL140989A0 (en) |
MY (1) | MY133564A (en) |
NZ (1) | NZ523651A (en) |
PE (1) | PE20011294A1 (en) |
Families Citing this family (35)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2001271784A1 (en) * | 2000-07-06 | 2002-01-21 | Wyeth | Therapy for prosthesis-related bone degeneration |
CA2414111A1 (en) * | 2000-07-06 | 2002-01-17 | Wyeth | Use of substituted indole compounds for increasing nitric oxide synthase activity |
US20080249183A1 (en) * | 2001-11-29 | 2008-10-09 | Steiner Mitchell S | Treatment of androgen-deprivation induced osteoporosis |
US20070197664A1 (en) * | 2001-11-29 | 2007-08-23 | Steiner Mitchell S | Prevention and treatment of androgen-deprivation induced osteoporosis |
US20060269611A1 (en) * | 2001-11-29 | 2006-11-30 | Steiner Mitchell S | Prevention and treatment of androgen-deprivation induced osteoporosis |
US7071210B2 (en) * | 2002-07-02 | 2006-07-04 | Pfizer Inc. | CETP inhibitors in combination with antihypertensive agents and uses thereof |
WO2005007110A2 (en) * | 2003-07-11 | 2005-01-27 | Pro-Pharmaceuticals, Inc. | Compositions and methods for hydrophobic drug delivery |
US20050053664A1 (en) * | 2003-09-08 | 2005-03-10 | Eliezer Zomer | Co-administration of a polysaccharide with a chemotherapeutic agent for the treatment of cancer |
EP1718146A2 (en) * | 2004-02-13 | 2006-11-08 | Pro-Pharmaceuticals, Inc. | Compositions and methods used to treat acne and candida |
EP1749017A2 (en) * | 2004-05-27 | 2007-02-07 | MIGENIX Corp. | Compounds and methods for cytoprotection |
US7772271B2 (en) | 2004-07-14 | 2010-08-10 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
US7781478B2 (en) | 2004-07-14 | 2010-08-24 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
US7868037B2 (en) | 2004-07-14 | 2011-01-11 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
US7645881B2 (en) | 2004-07-22 | 2010-01-12 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
WO2006017417A2 (en) * | 2004-08-02 | 2006-02-16 | Pro-Pharmaceuticals, Inc. | Compositions and methods for the enhancement of chemotherapy with microbial cytotoxins |
US7901710B2 (en) | 2005-08-04 | 2011-03-08 | Vertical Pharmaceuticals, Inc. | Nutritional supplement for use under physiologically stressful conditions |
US7998500B2 (en) | 2005-08-04 | 2011-08-16 | Vertical Pharmaceuticals, Inc. | Nutritional supplement for women |
US8263137B2 (en) | 2005-08-04 | 2012-09-11 | Vertical Pharmaceuticals, Inc. | Nutritional supplement for women |
US8202546B2 (en) | 2005-08-04 | 2012-06-19 | Vertical Pharmaceuticals, Inc. | Nutritional supplement for use under physiologically stressful conditions |
US8501690B2 (en) * | 2010-04-30 | 2013-08-06 | John G. Stark | Use of selective estrogen receptor modulator for joint fusion and other repair or healing of connective tissue |
EP3205648A1 (en) | 2010-06-10 | 2017-08-16 | Seragon Pharmaceuticals, Inc. | Estrogen receptor modulators and uses thereof |
WO2013090829A1 (en) | 2011-12-14 | 2013-06-20 | Aragon Pharmaceuticals, Inc. | Estrogen receptor modulators and uses thereof |
CN108366996B (en) | 2015-10-01 | 2021-04-09 | 奥列马制药公司 | tetrahydro-1H-pyridine [3,4-b ] indole antiestrogens |
EP3386500B1 (en) | 2015-12-09 | 2022-09-07 | The Board of Trustees of the University of Illinois | Benzothiophene-based selective estrogen receptor downregulators |
WO2017197055A1 (en) | 2016-05-10 | 2017-11-16 | C4 Therapeutics, Inc. | Heterocyclic degronimers for target protein degradation |
CN109562113A (en) | 2016-05-10 | 2019-04-02 | C4医药公司 | Loop coil degron body for target protein degradation |
EP3455218A4 (en) | 2016-05-10 | 2019-12-18 | C4 Therapeutics, Inc. | C3-carbon linked glutarimide degronimers for target protein degradation |
AU2017290748A1 (en) | 2016-07-01 | 2019-01-17 | G1 Therapeutics, Inc. | Pyrimidine-based antiproliferative agents |
WO2018081168A2 (en) | 2016-10-24 | 2018-05-03 | The Board Of Trustees Of The University Of Illinois | Benzothiophene-based selective mixed estrogen receptor downregulators |
JP7229162B2 (en) | 2017-01-06 | 2023-02-27 | ジー1 セラピューティクス, インコーポレイテッド | Combination therapy for cancer treatment |
CN110913861B (en) | 2017-06-29 | 2024-01-09 | G1治疗公司 | Morphological forms of G1T38 and methods of making the same |
CN113453679A (en) | 2018-12-20 | 2021-09-28 | C4医药公司 | Targeted protein degradation |
WO2024030968A1 (en) | 2022-08-03 | 2024-02-08 | Brystol-Myers Squibb Company | Compounds for modulating ret protein |
WO2024097980A1 (en) | 2022-11-04 | 2024-05-10 | Bristol-Myers Squibb Company | Ret-ldd protein inhibitors |
WO2024097989A1 (en) | 2022-11-04 | 2024-05-10 | Bristol-Myers Squibb Company | Ret-ldd protein degraders |
Family Cites Families (16)
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JPS5612114B2 (en) * | 1974-06-07 | 1981-03-18 | ||
GB2126576B (en) * | 1982-06-25 | 1985-06-19 | Farmos Group Limited | Alkane and alkene derivatives |
US4681893A (en) * | 1986-05-30 | 1987-07-21 | Warner-Lambert Company | Trans-6-[2-(3- or 4-carboxamido-substituted pyrrol-1-yl)alkyl]-4-hydroxypyran-2-one inhibitors of cholesterol synthesis |
NO177005C (en) * | 1988-01-20 | 1995-07-05 | Bayer Ag | Analogous process for the preparation of substituted pyridines, as well as intermediates for use in the preparation |
CA2040996A1 (en) * | 1990-05-02 | 1991-11-03 | Robert L. Albright | Composition and method for controlling cholesterol |
ATE213946T1 (en) * | 1991-12-18 | 2002-03-15 | COMPOSITION CONTAINING FORMOTEROL AND BUDESONIDE | |
US5447922A (en) * | 1994-08-24 | 1995-09-05 | Bristol-Myers Squibb Company | α-phosphonosulfinic squalene synthetase inhibitors |
US5552412A (en) | 1995-01-09 | 1996-09-03 | Pfizer Inc | 5-substitued-6-cyclic-5,6,7,8-tetrahydronaphthalen2-ol compounds which are useful for treating osteoporosis |
UA51676C2 (en) | 1995-11-02 | 2002-12-16 | Пфайзер Інк. | (-)cis-6(S)-phenyl-5(R)-[4-(2-pyrrolidin-I-ylethoxy)phenyl]-5,6,7,8-tetrahydronaphthalen-2-ol D-tartrate, a method of its preparation, method of THE treatment OF diseases medicated by agonists of estrogen and a pharmaceutical composition |
HN1996000101A (en) | 1996-02-28 | 1997-06-26 | Inc Pfizer | COMBINED THERAPY FOR OSTEOPOROSIS |
IL120266A (en) | 1996-02-28 | 2005-05-17 | Pfizer | Use of estrogen antagonists and estrogen agonists in the preparation of medicaments for inhibiting pathological conditions |
ZA979644B (en) | 1996-10-28 | 1998-04-28 | Novo Nordisk As | Heterocyclic compounds, compositions and uses. |
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US6653297B1 (en) | 1997-07-03 | 2003-11-25 | Medical College Of Hampton Roads | Control of selective estrogen receptor modulators |
WO1999045923A1 (en) * | 1998-03-13 | 1999-09-16 | Merck & Co., Inc. | Methods of inhibiting bone resorption |
-
2000
- 2000-12-28 CO CO00098264A patent/CO5251465A1/en not_active Application Discontinuation
-
2001
- 2001-01-18 IL IL14098901A patent/IL140989A0/en unknown
- 2001-01-22 MY MYPI20010286A patent/MY133564A/en unknown
- 2001-01-22 EP EP01300527A patent/EP1123717A3/en not_active Withdrawn
- 2001-01-22 KR KR1020010003519A patent/KR20010083135A/en not_active Application Discontinuation
- 2001-01-23 US US09/767,625 patent/US6756401B2/en not_active Expired - Fee Related
- 2001-01-24 PE PE2001000079A patent/PE20011294A1/en not_active Application Discontinuation
- 2001-01-24 JP JP2001015626A patent/JP2001206845A/en active Pending
- 2001-01-24 CA CA002332214A patent/CA2332214A1/en not_active Abandoned
- 2001-01-25 NZ NZ523651A patent/NZ523651A/en unknown
- 2001-01-25 AU AU16675/01A patent/AU780568B2/en not_active Ceased
- 2001-01-25 HU HU0100388A patent/HUP0100388A3/en unknown
-
2004
- 2004-05-06 US US10/840,577 patent/US20040259886A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
AU780568B2 (en) | 2005-04-07 |
HUP0100388A3 (en) | 2006-02-28 |
CO5251465A1 (en) | 2003-02-28 |
EP1123717A3 (en) | 2003-10-15 |
EP1123717A2 (en) | 2001-08-16 |
KR20010083135A (en) | 2001-08-31 |
MY133564A (en) | 2007-11-30 |
HU0100388D0 (en) | 2001-03-28 |
US6756401B2 (en) | 2004-06-29 |
US20040259886A1 (en) | 2004-12-23 |
HUP0100388A2 (en) | 2003-08-28 |
JP2001206845A (en) | 2001-07-31 |
CA2332214A1 (en) | 2001-07-26 |
AU1667501A (en) | 2001-08-02 |
US20030162807A1 (en) | 2003-08-28 |
NZ523651A (en) | 2004-06-25 |
IL140989A0 (en) | 2002-02-10 |
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